Trial Search Results

A Study to Compare the Administration of Pembrolizumab After Surgery Versus Administration Both Before and After Surgery for High-Risk Melanoma

This phase II trial studies how pembrolizumab works before and after surgery in treating patients with stage III-IV high-risk melanoma. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.. Giving pembrolizumab before and after surgery may work better compared to after surgery alone in treating melanoma.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

National Cancer Institute (NCI)

Stanford Investigator(s):

Intervention(s):

  • Biological: Pembrolizumab
  • Procedure: Therapeutic Conventional Surgery

Phase:

Phase 2

Eligibility


Inclusion Criteria:

   - STEP 1 REGISTRATION (RANDOMIZATION)

   - Patients must have resectable melanoma in order to be eligible for this study.
   Patients must have clinically detectable stage III (clinically detectable N1b, N1c,
   N2b, N2c, N3b and N3c) or stage IV resectable melanoma. Patients with melanoma of
   mucosal or acral origin are eligible. Patients with melanoma of uveal origin are not
   eligible. Patients with a history of brain metastases are not eligible. Clinically
   detectable is defined as disease that is apparent and measurable via physical
   examination or radiographic imaging.

   - Patients are eligible for this trial either at initial presentation of their melanoma
   or at the time of the first detected nodal, satellite/in-transit, distant metastases,
   or recurrent disease in prior lymphadenectomy basin or distant site. Nodal,
   satellite/in-transit metastasis, distant metastases or disease in a prior complete
   lymphadenectomy basin must have been confirmed histologically by hematoxylin (H) &
   eosin (E) stained slides.

   - Patients with multiple regional nodal basin involvement are eligible. Gross or
   microscopic extracapsular nodal extension is permitted.

   - Patients must have histologically proven stage IIIB or higher. This would entail
   pathologic confirmation beyond the primary or initial diagnosis of melanoma involving
   fine needle aspiration cytology or biopsy confirmation of any N-category or M-category
   resectable site.

   - Patients may have received prior radiation therapy, including after prior surgical
   resection. All adverse events associated with prior surgery and radiation therapy must
   have resolved to =< grade 1 prior to randomization.

   - All patients must have disease status documented by a complete physical examination
   and imaging studies within 42 days prior to randomization. Imaging studies must
   include a CT of the chest, abdomen and pelvis with intravenous contrast (unless
   contraindicated). For patients with melanoma arising from the head and neck, dedicated
   neck imaging (CT with intravenous contrast is required. If the patient has unknown
   primary with disease in the axilla, neck imaging is required CT imaging must be done
   with intravenous contrast if there are no contraindications for it. Extremity
   melanomas must be imaged using CT with intravenous contrast or MRI with and without
   gadolinium

      - Note: PET-CT scans are NOT acceptable to establish eligibility. Non-iodinated CT
      scans that are part of common PET-CT imaging protocols do not provide contrast
      for difficult to ascertain areas such as the neck and liver, and do not provide
      enough CT detail to perform appropriate RECIST 1.1 measurements. As such, a
      PET-CT with non-contrast CT or non-diagnostic quality CT images is considered
      insufficient for the detection of melanoma.

   - All patients must have a CT or magnetic resonance imaging (MRI) of the brain within 42
   days prior to randomization. The brain CT or MRI should be performed with intravenous
   contrast (unless contraindicated).

   - Absolute neutrophil count (ANC) >= 1,500/microliter (mcL) (within 42 days prior to
   randomization).

   - Platelets >= 100,000/mcL (within 42 days prior to randomization).

   - Hemoglobin >= 10 g/dL (within 42 days prior to randomization).

   - Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) (except patients
   with Gilbert's syndrome, who must have a total bilirubin < 3.0 mg/dL) (within 42 days
   prior to randomization).

   - Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and
   serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2 x
   IULN (within 42 days prior to randomization).

   - Alkaline phosphatase =< 2 x IULN (within 42 days prior to randomization).

   - Patients must have lactate dehydrogenase (LDH) performed within 42 days prior to
   randomization.

   - Patients must have adequate renal function as evidenced by calculated creatinine
   clearance > 30 mL/min. The creatinine level (mg/dL) used in the calculation must be
   obtained within 42 days prior to randomization.

   - Patients must have Zubrod performance status =< 2.

   - Patients known to be human immunodeficiency virus (HIV) positive are eligible if they
   meet the following criteria within 30 days prior to randomization: stable and adequate
   CD4 counts (>= 350 mm^3), and serum HIV viral load of < 25,000 IU/ml. Patients may be
   on or off anti-viral therapy so long as they meet the CD4 count criteria.

   - Prior malignancy is allowed providing it does not require concurrent therapy.

   - Women of childbearing potential must have a negative urine or serum pregnancy test
   within 28 days prior to randomization. Women/men of reproductive potential must have
   agreed to use an effective contraceptive method for the course of the study through
   120 days after the last dose of study medication. Should a woman become pregnant or
   suspect she is pregnant while she or her partner is participating in this study, she
   should inform her treating physician immediately. A woman is considered to be of
   "reproductive potential" if she has had menses at any time in the preceding 12
   consecutive months. In addition to routine contraceptive methods, "effective
   contraception" also includes heterosexual celibacy and surgery intended to prevent
   pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy,
   bilateral oophorectomy, or bilateral tubal ligation. However, if at any point a
   previously celibate patient chooses to become heterosexually active during the time
   period for use of contraceptive measures outlined in the protocol, he/she is
   responsible for beginning contraceptive measures. Patients must not be pregnant or
   nursing due to unknown teratogenic side effects.

   - Patients must be deemed medically fit to undergo surgery by the treating
   medical/surgical team.

   - Patients must be willing to submit the following surgical specimens: either all tissue
   blocks from the surgical specimen or two slides per block ([1] hematoxylin and eosin
   [H&E] slide and [1] unstained slide OR [2] unstained slides if H&E stained slides
   cannot be provided).

   - Patients must be offered the opportunity to participate in specimen banking.

   - Patients must be informed of the investigational nature of this study and must sign
   and give written informed consent for this protocol in accordance with institutional
   and federal guidelines.

   - As a part of the Oncology Patient Enrollment Network (OPEN) randomization process the
   treating institution's identity is provided in order to ensure that the current
   (within 365 days) date of institutional review board approval for this study has been
   entered in the system.

   - STEP 2 REGISTRATION (SURGERY)

   - Patients randomized to arm 2 (neoadjuvant arm) must be willing to submit tissue to
   determine pathologic response regardless of number of pre-operative doses of MK-3475
   (pembrolizumab) received. Determination of pathologic response cannot be done on less
   than the full surgical specimen.

   - Patients must have disease assessments by PET-CT with iodinated CT contrast (i.e.
   diagnostic quality CT) or CT chest/abdomen/pelvis with IV contrast, and neck CT with
   IV contrast if primary head and neck melanoma, performed within 42 days (and no more
   than 49 days) before the planned date of surgery. MRI combined with non-contrast CT is
   an acceptable alternative for patients with CT contrast allergy, but imaging must
   encompass total body.

   - Patients must register to step 2 within 17 days prior to planned date of surgery.

   - STEP 3 REGISTRATION (ADJUVANT THERAPY)

   - Patients must have undergone surgery prior to Step 3 registration. The Step 2 surgery
   must have completely resected their melanoma.

      - Patients with gross positive residual disease at the time of surgery do not
      qualify as having disease-free status, and, therefore, such patients are not
      eligible to register for adjuvant therapy.

      - Patients with microscopic residual disease (i.e., positive margins) can be
      treated with re-excision or radiation, per site discretion, to render the patient
      disease-free prior to registration of adjuvant therapy.

      - Disease-free status must be documented by a complete physical examination and
      radiographic imaging studies within 42 days prior to Step 3 registration. Imaging
      studies must include a total body PET-CT that is of diagnostic quality (i.e.,
      iodinated contrast), or a CT of the chest, abdomen, and pelvis.

      - For patients with melanoma arising from the head and neck, dedicated neck imaging
      (CT with IV contrast with PET-CT through the region) is required.

      - If the patient has had unknown primary with disease in the axilla, neck imaging
      is required to assure the region is clear of cancer.

      - CT imaging should be done with intravenous contrast if there are no
      contraindications for it.

      - Any other clinically-indicated imaging studies if performed (e.g., bone scan)
      must show no evidence of disease.

   - Patients must be registered to step 3 no more than 84 days after date of surgery.

   - Patients with R0 or R1 resections must have disease-free status documented by a
   complete physical examination and imaging studies within 42 days prior to step 3
   registration. These patients must have disease assessments by CT chest/abdomen/pelvis
   with IV contrast, and neck CT with IV contrast if primary head and neck melanoma. MRI
   combined with non-contrast CT is an acceptable alternative for patients with CT
   contrast allergy, but imaging must encompass total body.

   - Patients with R2 resections are not eligible for step 3 and must be removed from study
   treatment

Exclusion Criteria:

   - Patients must not have received previous neoadjuvant treatment for their melanoma.
   Patients may have received prior non-immunotherapy adjuvant therapy. Patients must not
   have had prior immunotherapy including, but not limited to ipilimumab, interferon
   alfa-2b, high dose interleukin (IL)-2, pegylated-interferon (PEG-IFN), anti-PD-1,
   anti-PD-L1 intra-tumoral, or vaccine therapies. Patients must not be planning to
   receive any of the prohibited therapies during treatment phases on the study.

   - Patients must not be planning to receive concomitant other biologic therapy, hormonal
   therapy, other chemotherapy, surgery, while on protocol therapy.

   - Patients must not have a history of (non-infectious) pneumonitis that required
   steroids or current pneumonitis.

   - Patients must not have an active infection requiring systemic therapy.

   - Patients must not have active autoimmune disease that has required systemic treatment
   in past 2 years (i.e., with use of disease modifying agents, corticosteroids or
   immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or
   physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency,
   etc.) is not considered a form of systemic treatment.

   - Patients must not have received live vaccines within 42 days prior to randomization.
   Examples of live vaccines include, but are not limited to, the following: measles,
   mumps, rubella, chicken pox, shingles, yellow fever, rabies, Bacillus Calmette-Guerin
   (BCG), and typhoid (oral) vaccine. Seasonal influenza vaccines for injection are
   generally killed virus vaccines and are allowed; however, intranasal influenza
   vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed.

      - NOTE: The COVID-19 vaccines (currently available and those in the pipeline for
      FDA emergency use authorization or FDA approval) do not contain live virus, and
      therefore, COVID-19 vaccination does not affect or preclude eligibility for the
      S1801 trial. For patients who have undergone lymphadenectomy, vaccines should be
      delivered to a limb with an intact lymph node basin (Sentinel lymph node biopsy
      in a limb is acceptable). The vaccine should not be administered in a limb that
      has undergone lymphadenectomy.

   - Patients must not have known active hepatitis B virus (HBV) or hepatitis C virus (HCV)
   infection prior to randomization. Note: No testing for hepatitis B and hepatitis C is
   required unless mandated by local health authority.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Lisa Y Zhou
650-736-4112
Recruiting